LS-2-P-2137 Phosphatidylinositol 4,5-bisphosphate interacts with lysine-specific histone demethylase 1 in the nucleus.

The eukaryotic nucleus is a highly structured cellular compartment composed mainly of proteins and nucleic acids. In addition to these abundant molecules, the nuclear interior also contains minor components such as phosphoinositides. Phosphoinositides are phosphorylated forms of phosphatidylinositol - a negatively charged glycerol-based phospholipid. In the cytoplasm, phosphoinositides are well known signalling molecules involved in regulation of membrane dynamics, cell architecture and motility, modulation of ion channels and transporters, or generation of second messengers. Moreover, it has been suggested that phosphoinositide signalling occurs also in the cell nucleus. Phosphatidylinositol 4,5-bisphosphate (PIP2) localizes to nucleoli, nuclear speckles, and small foci in the nucleoplasm. It was shown that nuclear PIP2 is required for DNA transcription, pre-mRNA processing, and export of mRNA to the cytoplasm. Here we present a novel PIP2 binding protein - lysine-specific histone demethylase 1 (LSD1). LSD1 was previously shown as a potential PIP2 interacting protein using neomycin extraction. We confirmed that LSD1 forms a complex with PIP2 within the nucleus and that the LSD1-PIP2 interaction is direct. As shown by structured illumination microscopy, LSD1 localizes to the edges of nuclear speckles and co-localizes with PIP2 in small PIP2 foci in the nucleoplasm. These data indicate that PIP2 through LSD1 may regulate histone demethylation and therefore may play a role in regulation of gene expression.